The activity of proteolytic emzymes released from damaged pulmonary tissue may produce destruction of pulmonary tissue. The proposed project will compare and contrast the effects on dog, rat or hamster lung, of aerosolized papain and aerosolized extracts made from leukocyte homogenates, both of which have been reported to produce emphysema-like lesions in animal lung tissue. The release of proteolytic enzymes from leukocytes may produce a less severe emphysema than papain. The effects of exposing the animals to cigarette smoke for varying periods of time will be studied using both physiological measurements of blood gases and pulmonary mechanics and scanning electron microscopy as well as standard histologic examination of lung section. In addition, animals which have been treated with papain or leukocyte extract will be exposed to cigarette smoke in order to see if smoking increases the severity of pulmonary damage. A panel of standards for papain emphysema in hamster has been devised. Correlation of these standards with scanning light microscopy will be done so that consistency of grading may be achieved.